It has been shown in our laboratory and others that the Auger effect accompanying 125I decay is extremely toxic when 125I is incorporated into cellular DNA in the form of iododeoxyuridine (125IUdR). We now propose to use the established cell culture test system to compare the toxicity of 125I when it is uniformly distributed throughout the cell in the form of iodoantipyrine with that of 125I affixed to DNA. In addition, the toxicity of other Auger electron emitting radionuclides (including 57 Co, 67Ga, 75Se, 99mTc, 11In, 113mIn and 201 T1) and some alpha emitters will be tested in the same system and compared with that of 125I. The intracellular distribution of various compounds labeled with these nuclides will be measured and its relationship to their biological consequences determined. This information will be used to establish the potential biohazards or therapeutic benefits of some of the compounds. The therapeutic efficacy of such compounds will be further examined and compared with 125IUdR in the mouse ascites tumor model previously established in this laboratory. We also propose to investigate the mechanisms and various aspects by which Auger effect causes biological damages. First, relative sensitivities of various cell lines to Auger electrons and low LET radiations will be compared and the differences related to their variations in nuclear size, DNA content, chromosome number and the cellular ability to repair single-strand breaks. Secondly, cytogenetic changes will be scored in synchronized cell cultures exposed to Auger and alpha emitters and the results interpreted in relation to their lethal effects. Thirdly, the effects of oxygen and anoxic sensitizers on the biological toxicity of Auger electrons will be determined. Lastly, an electron spin resonance study of 125IUdR will be initiated to elucidate the action of Auger electrons at the molecular level.